George S. Bloom

Education

  • BA, University of Pennsylvania
  • PhD, University of Pennsylvania
  • Postdoc, University of North Carolina
  • Postdoc, Worcester Foundation for Exp. Biol

Primary Appointment

  • Professor, Biology

Contact

Research Interest(s)

Alzheimer's Disease

Research Description

Research in our laboratory is now focused primarily on Alzheimer's disease (AD), the most common form of a group of neurodegenerative disorders known collectively as tauopathies. The histopathological hallmark of AD is the presence in brain of extracellular plaques of β-amyloid peptide fibrils, and intraneuronal neurofibrillary tangles, which are filaments composed of the protein, tau, and are found in all tauopathies. Despite the conspicuous appearance of plaques and tangles, a growing body of evidence points to their building blocks, β-amyloid and tau oligomers, as being the toxic molecular species that cause AD. For example, we have found that tau expression is required for several adverse effects of β-amyloid oligomers on neurons, including microtubules loss, ectopic re-rentry into the cell cycle and cytotoxicity. The goals of our work are to decipher the metabolic links that connect β-amyloid and tau to damage neurons, to define the structures and pathological properties of various types of β-amyloid and tau oligomers, and to develop effective therapeutic and diagnostic tools for AD.

Selected Publications

  • Amyloid-β and tau: the trigger and bullet in Alzheimer disease pathogenesis. JAMA neurology. 2014;71(4): 505-8. PMID: 24493463
  • Marbiah M, Harvey A, West B, Louzolo A, Banerjee P, Alden J, Grigoriadis A, Hummerich H, Kan H, Cai Y, Bloom G, Jat P, Collinge J, Klöhn P. Identification of a gene regulatory network associated with prion replication. The EMBO journal. 2014;33(14): 1527-47. PMID: 24843046
  • Ferrer-Acosta Y, Rodríguez-Cruz E, Orange F, De Jesús-Cortés H, Madera B, Vaquer-Alicea J, Ballester J, Guinel M, Bloom G, Vega I. EFhd2 is a novel amyloid protein associated with pathological tau in Alzheimer's disease. Journal of neurochemistry. 2013;125(6): 921-31. PMID: 23331044 | PMCID: PMC3676478
  • Seward M, Swanson E, Norambuena A, Reimann A, Cochran J, Li R, Roberson E, Bloom G. Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer's disease. Journal of cell science. 2013;126 1278-86. PMID: 23345405 | PMCID: PMC3635465
  • Wallrabe H, Cai Y, Sun Y, Periasamy A, Luzes R, Fang X, Kan H, Cameron L, Schafer D, Bloom G. IQGAP1 interactome analysis by in vitro reconstitution and live cell 3-color FRET microscopy. Cytoskeleton (Hoboken, N.J.). 2013;70(12): 819-36. PMID: 24124181 | PMCID: PMC3917506
  • Nussbaum J, Schilling S, Cynis H, Silva A, Swanson E, Wangsanut T, Tayler K, Wiltgen B, Hatami A, Rönicke R, Reymann K, Hutter-Paier B, Alexandru A, Jagla W, Graubner S, Glabe C, Demuth H, Bloom G. Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. Nature. 2012;485(7400): 651-5. PMID: 22660329 | PMCID: PMC3367389
  • Nussbaum J, Seward M, Bloom G. Alzheimer disease: a tale of two prions. Prion. 2012;7(1): 14-9. PMID: 22965142 | PMCID: PMC3609044
  • Bamburg J, Bloom G. Cytoskeletal pathologies of Alzheimer disease. Cell motility and the cytoskeleton. 2009;66(8): 635-49. PMID: 19479823 | PMCID: PMC2754410
  • Yan J, Yang Y, Zhang H, King C, Kan H, Cai Y, Yuan C, Bloom G, Hua X. Menin interacts with IQGAP1 to enhance intercellular adhesion of beta-cells. Oncogene. 2008;28(7): 973-82. PMID: 19079338 | PMCID: PMC2645484
  • Benseñor L, Kan H, Wang N, Wallrabe H, Davidson L, Cai Y, Schafer D, Bloom G. IQGAP1 regulates cell motility by linking growth factor signaling to actin assembly. Journal of cell science. 2007;120 658-69. PMID: 17264147
  • King M, Kan H, Baas P, Erisir A, Glabe C, Bloom G. Tau-dependent microtubule disassembly initiated by prefibrillar beta-amyloid. The Journal of cell biology. 2006;175(4): 541-6. PMID: 17101697 | PMCID: PMC2064590
  • Mundy D, Machleidt T, Ying Y, Anderson R, Bloom G. Dual control of caveolar membrane traffic by microtubules and the actin cytoskeleton. Journal of cell science. 2002;115 4327-39. PMID: 12376564
  • Bloom G, Goldstein L. Cruising along microtubule highways: how membranes move through the secretory pathway. The Journal of cell biology. 1998;140(6): 1277-80. PMID: 9508761 | PMCID: PMC2132669
  • Bashour A, Fullerton A, Hart M, Bloom G. IQGAP1, a Rac- and Cdc42-binding protein, directly binds and cross-links microfilaments. The Journal of cell biology. 1997;137(7): 1555-66. PMID: 9199170 | PMCID: PMC2137827
  • Conrad P, Smart E, Ying Y, Anderson R, Bloom G. Caveolin cycles between plasma membrane caveolae and the Golgi complex by microtubule-dependent and microtubule-independent steps. The Journal of cell biology. 1995;131(6): 1421-33. PMID: 8522601 | PMCID: PMC2120680
  • Lippincott-Schwartz J, Cole N, Marotta A, Conrad P, Bloom G. Kinesin is the motor for microtubule-mediated Golgi-to-ER membrane traffic. The Journal of cell biology. 1995;128(3): 293-306. PMID: 7844144 | PMCID: PMC2120357
  • Vallee R, Bloom G. Mechanisms of fast and slow axonal transport. Annual review of neuroscience. 1991;14 59-92. PMID: 1709561
  • Hirokawa N, Pfister K, Yorifuji H, Wagner M, Brady S, Bloom G. Submolecular domains of bovine brain kinesin identified by electron microscopy and monoclonal antibody decoration. Cell. 1989;56(5): 867-78. PMID: 2522351
  • Pfister K, Wagner M, Stenoien D, Brady S, Bloom G. Monoclonal antibodies to kinesin heavy and light chains stain vesicle-like structures, but not microtubules, in cultured cells. The Journal of cell biology. 1989;108(4): 1453-63. PMID: 2522455 | PMCID: PMC2115510
  • Bloom G, Luca F, Vallee R. Microtubule-associated protein 1B: identification of a major component of the neuronal cytoskeleton. Proceedings of the National Academy of Sciences of the United States of America. 1985;82(16): 5404-8. PMID: 3895231 | PMCID: PMC390577